mDia1 (also known as Dia1, Drf1 for Diaphanous-related formin-1, Diaph1, KIAA4062, p140mDia, mKIAA4062, or D18Wsu154e) is a member of the protein family called the formins and is a Rho effector. It is the mouse version of the diaphanous homolog 1 of Drosophila. mDia1 localizes to cells' mitotic spindle and midbody, plays a role in stress fiber and filopodia formation, phagocytosis, activation of serum response factor, formation of adherens junctions, and it can act as a transcription factor. mDia1 accelerates actin nucleation and elongation by interacting with barbed ends (fast-growing ends) of actin filaments. The gene encoding mDia1 is located on Chromosome 18 of Mus musculus and named Diap1. mDia1 is highly homologous to Drosophila diaphanous, regulating the cytokinetic ring during cytokinesis. Homologues in other species are known as well, like the human DIAP1, budding yeast Bni1 or fission yeast Cdc12p. The gene has been knocked-out in mice. Structure The product of the Diap1 (Diaph1) gene consists of 1255 amino acids resulting in a molecular weight of 139,343 daltons. The mDia1 polypeptide chain can be divided into four protein domains: GBD/FH3 (Rho GTPase-binding domain/formin homology 3)domain (366 amino acids long): positions 75-440 FH1 (formin homology 1) domain (162 amino acids long): positions 586-747 FH2 (formin homology 2) domain (403 amino acids long): positions 752-1154 DAD (diaphanous autoregulatory domain) (29 amino acids long): positions 1177-1205 Three supplementary domains were discovered: coiled coil (103 amino acids long): positions 460-562 coiled coil (153 amino acids long): positions 1027-1179 Arg/Lys-rich domain (4 amino acids long): positions: 1196-1199 The active region of the C terminus consists of formin homology 1 and 2 (FH1 and FH2) and the Dia autoregulatory domain (DAD). The FH1 domain is predicted to be rope-like and it contains binding sites for profilin-actin complexes. The adjacent FH2 domain forms together with the FH2 domain of a second mDia1 molecule a head-to-tail doughnut shaped dimer that encircles the barbed end of an actin filament. Thus the FH2 domain has the ability to dimerize. The N terminus consists of a Rho GTPase-binding domain (GBD), which is joint to the formin homology 3 (FH3). DAD can mediate autoinhibition through interactions with the Dia inhibitory domain (DID), which is a subdomain of the GDB/FH3 domain (see section Regulation). Regulation Autoinhibition is achieved through binding of the C-terminal DAD to the N-terminal DID. This interaction inhibits the ability of FH2 to nucleate actin assembly. Rho-GTP binds to the